Guillain-Barré syndrome in a local area in Japan, 2006-2015: an epidemiological and clinical study of 108 patients.

BACKGROUND AND PURPOSE: Many epidemiological studies of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) have been conducted in Europe and America. In contrast, epidemiological studies are rare in Asia where the GBS subtypes differ from those in Western countries. This study was undertaken to clarify the incidence of GBS and FS in a local area in Japan as well as their seasonal trends. METHOD: Seventy-one GBS and 37 FS patients were recorded from 2006 to 2015 in an area of approximately 1.5 million inhabitants in Japan. The incidence, seasonal trends and clinical features of GBS and FS were examined. RESULTS: The incidence rate of GBS was 0.42 cases per 100 000 person-years and that of FS was 0.22 cases per 100 000 person-years. The incidence of GBS increased with age and FS affected predominantly patients aged from 45 to 64 years old. There was some seasonal clustering of acute motor axonal neuropathy (AMAN) and FS in spring and summer, but it was not significant. AMAN and FS patients had a high frequency of preceding infection (AMAN, 68% gastrointestinal infection; FS, 65% upper respiratory infection). Antecedent respiratory infection was significantly associated with FS as an outcome. Serum antibodies to ganglioside GM1 were detected in 71% of AMAN patients and antibodies to GQ1b were detected in 81% of FS patients. CONCLUSIONS: Our study offers evidence of a lower incidence of GBS and a higher incidence of FS in a local area in Japan than in Western countries.

Clinical and mutational spectrum of Japanese patients with Charcot-Marie-Tooth disease caused by GDAP1 variants.

BACKGROUND: Mutations in GDAP1 are responsible for heterogeneous clinical and electrophysiological phenotypes of Charcot-Marie-Tooth disease (CMT), with autosomal dominant or recessive inheritance pattern. The aim of this study is to identify the clinical and mutational spectrum of CMT patients with GDAP1 variants in Japan. MATERIALS AND METHODS: From April 2007 to October 2014, using three state-of-art technologies, we conducted gene panel sequencing in a cohort of 1,030 patients with inherited peripheral neuropathies (IPNs), and 398 mutation-negative cases were further analyzed with whole-exome sequencing. RESULTS: We identified GDAP1 variants from 10 patients clinically diagnosed with CMT. The most frequent recessive variant in our cohort (5/10), c.740C>T (p.A247V), was verified to be associated with a founder event. We also detected three novel likely pathogenic variants: c.928C>T (p.R310W) and c.546delA (p.E183Kfs*23) in Case 2 and c.376G>A (p.E126K) in Case 8. Nerve conduction study or sural nerve biopsy of all 10 patients indicated axonal type peripheral neuropathy. CONCLUSION: We identified GDAP1 variants in approximately 1% of our cohort with IPNs, and established a founder mutation in half of these patients. Our study originally described the mutational spectrum and clinical features of GDAP1-related CMT patients in Japan.

Intramuscular dissociation of echogenicity in the triceps surae characterizes sporadic inclusion body myositis.

BACKGROUND AND PURPOSE: Differential diagnosis of sporadic inclusion body myositis (s-IBM) and polymyositis (PM)/dermatomyositis (DM) is difficult and can affect proper disease management. Detection of heterogeneous muscular involvement in s-IBM by muscle sonography could be a unique diagnostic feature. METHODS: Sonography of the lower leg and forearm was performed in patients with s-IBM, PM/DM and control subjects (n = 11 each). Echo intensities (EIs) of the adjacent muscles [medial head of the gastrocnemius versus soleus and the flexor digitorum profundus (FDP) versus flexor carpi ulnaris (FCU)] were scored by three blinded raters. The mean EIs of these muscles were compared using computer-assisted histogram analysis. RESULTS: Both evaluation methods showed high echoic signals in the gastrocnemius of patients with s-IBM. EIs were significantly different between the gastrocnemius and soleus in patients with s-IBM, but not in those with DM/PM and the controls. In the forearm, although the EI of the FDP was higher in the s-IBM group than in the other groups, the EI differences between the FDP and FCU did not differ significantly between disease groups. The difference in area under the curves to differentiate between s-IBM and DM/PM was greatest between the gastrocnemius-soleus EIs (0.843; P = 0.006). CONCLUSIONS: High echoic signals in the medial gastrocnemius compared with those of the soleus are suggestive of s-IBM over PM/DM.

Simulated Cuspal Deflection and Flexural Properties of Bulk-Fill and Conventional Flowable Resin Composites.

CLINICAL RELEVANCE: Some bulk-fill flowable resin composites produce less cuspal deflection than a conventional incrementally filled flowable resin composites. SUMMARY: Objective: This study investigated simulated cuspal deflection and flexural properties of bulk-fill and conventional flowable resin composites.Methods and Materials: Five bulk-fill and six conventional flowable resin composites were evaluated. Aluminium blocks with a mesio-occlusal-distal cavity were prepared and randomly divided into groups for each of the different measurement techniques and were further subdivided according to the type of flowable resin composite. The simulated cuspal deflection caused by the polymerization of resin composite within an aluminium block was measured using a highly accurate submicron digimatic micrometer or a confocal laser scanning microscope (CLSM). In addition, the flexural properties of tested resin composites were measured to investigate the relation between cuspal deflection and flexural properties, and the resin composites were observed using scanning electron microscopy.Results: Simulated cuspal deflection of some bulk-fill flowable resin composites was found to be significantly lower than or similar to those for conventional counterparts, regardless of the measurement method. There were statistically significant differences in flexural properties depending on the material, regardless of the type of flowable resin composite. Pearson correlation analysis did not reveal a statistically significant relationship between flexural properties and cuspal deflection.Conclusion: These results indicate that some bulk-fill flowable resin composites exhibit lower cuspal deflection with the bulk-filling technique than is shown by conventional flowable resin composites using the incremental filling technique. Simulated cuspal deflection can be measured using either a micrometer or CLSM, but this experiment failed to show a significant relationship between cuspal deflection and flexural properties of flowable resin composites.

Implications of prodromal angina pectoris in anterior wall acute myocardial infarction: acute angiographic findings and long-term prognosis.

OBJECTIVES: This study was undertaken to assess how prodromal angina affects long-term prognosis after acute myocardial infarction. BACKGROUND: Although it has been reported that prodromal angina occurring shortly before the onset of acute myocardial infarction has protective effects against ischemia, its implication for long-term prognosis remains unclear. METHODS: We studied consecutive 350 patients with anterior myocardial infarction who underwent coronary angiography within 24 h after the onset of chest pain. Follow-up was achieved for 340 patients (97%). RESULTS: Eighty-nine patients had one or more episodes of angina within 24 h before infarction. On initial angiography, patients with prodromal angina in the 24 h before infarction had a patent infarct-related artery more frequently than did those without prodromal angina (34% vs. 22%, p = 0.03). Among 213 patients who underwent thrombolytic therapy for an occluded infarct-related artery, reperfusion was more frequently achieved in patients with prodromal angina in the 24 h before infarction (76% vs. 56%, p = 0.01). Prodromal angina in the 24 h before infarction was associated with a lower in-hospital mortality rate (6% vs. 14%, p = 0.02) and better 5-year survival (p = 0.009). There was no significant difference in survival between patients with previous angina at any time (n = 202) and those without. Multivariate analysis showed that prodromal angina in the 24 h before infarction was an independent factor related to 5-year survival after acute myocardial infarction (odds ratio 0.49, p = 0.04). CONCLUSIONS: Prodromal angina occurring shortly before the onset of infarction, but not previous angina itself, has a beneficial effect on long-term prognosis after infarction, suggesting a relation to ischemic preconditioning.

Diabetes mellitus prevents ischemic preconditioning in patients with a first acute anterior wall myocardial infarction.

OBJECTIVES: This study was undertaken to assess whether prodromal angina could have beneficial effects in diabetic patients with acute myocardial infarction (AMI). BACKGROUND: Prodromal angina occurring shortly before the onset of AMI is associated with favorable outcomes by the mechanism of ischemic preconditioning. However, little is known about the impact of diabetes on ischemic preconditioning. METHODS: We studied 611 patients with a first anterior wall AMI who underwent emergency catheterization within 12 h after the onset of chest pain: 490 patients without diabetes and 121 patients with non-insulin treated diabetes. Prodromal angina was defined as angina episode(s) occurring within 24 h before the onset of AMI. Serial contrast left ventriculograms were obtained in 424 patients at the time of acute and predischarge catheterization. RESULTS: In non-diabetic patients, prodromal angina was associated with lower peak creatine kinase (CK) value (3,068 +/- 2,647 IU/l vs. 3,601 +/- 2,462 IU/l, p = 0.037), larger increase in left ventricular ejection fraction (LVEF) (10.1 +/- 13.0% vs. 5.8 +/- 13.4%, p = 0.004) and lower in-hospital mortality (3.4% vs. 9.3%, p = 0.015). On the contrary, in diabetic patients, there was no significant difference in peak CK value (3,382 +/- 2,520 IU/l vs. 3,233 +/- 2,412 IU/l, p = NS), the change in LVEF (6.7 +/- 13.8% vs. 7.1 +/- 12.4%, p = NS) and in-hospital mortality (8.8% vs. 11.0%, p = NS) between patients with and patients without prodromal angina. CONCLUSIONS: Prodromal angina limited infarct size, enhanced recovery of LV function and improved survival in non-diabetic patients with AMI. However, such beneficial effects of prodromal angina were not observed in diabetic patients, suggesting that diabetes might prevent ischemic preconditioning.

Usefulness of directional coronary atherectomy in patients with acute anterior myocardial infarction.

To assess the usefulness of directional coronary atherectomy (DCA) in acute myocardial infarction (AMI), 139 consecutive patients with anterior wall AMI undergoing successful catheter intervention were studied. The reocclusion rate was significantly lower in the last 70 patients who underwent DCA as aggressively as possible compared with the first 69 patients treated with coronary balloon angioplasty (12.1% vs 3.0%, p <0.05).

Time course of impaired coronary flow reserve after reperfusion in patients with acute myocardial infarction.

To evaluate the time course of coronary flow reserve after reperfusion, 14 patients with a first anterior wall acute myocardial infarction who underwent successful coronary angioplasty within 6 hours after symptom onset were studied. After angioplasty, coronary flow reserve of the left anterior descending artery was measured with a coronary Doppler guidewire and intravenous dipyridamole (0.56 mg/kg over 4 minutes). Measurements were repeated at predischarge (16 +/- 3 days, n = 12) and at follow-up (6 +/- 3 months, n = 9). Patients with restenosis at the time of repeat catheterization were excluded. An additional 13 patients with normal angiograms served as reference patients. Coronary flow reserve was 1.33 +/- 0.29 after angioplasty. It increased to 1.88 +/- 0.36 at predischarge (p <0.01) and further to 2.34 +/- 0.38 at follow-up (p <0.01 vs after angioplasty and at predischarge, respectively). However, compared with reference patients (3.15 +/- 0.48), coronary flow reserve was significantly reduced in the infarct patients even at follow-up (p <0.01). In infarct patients, the infarct region wall motion was initially -3.86 +/- 0.67 SD/chord. It significantly improved to -2.07 +/- 1.04 SD/chord at predischarge (p <0.01) and to -1.67 +/- 1.43 SD/chord at follow-up (p <0.01). However, there was no significant relation between coronary flow reserve and region wall motion after angioplasty (r = 0.10), at predischarge (r = 0.35), and at follow-up (r = 0.28). Thus, coronary flow reserve is severely impaired early after reperfusion. Coronary flow reserve improves over 2 weeks, but the impairment persists at 6 months after acute myocardial infarction. The impairment of coronary flow reserve cannot be predicted by left ventricular function. Small sample size is a potential limitation of this study, and a larger study should be performed to confirm these findings.

Dual contrast magnetic resonance imaging with combined use of positive and negative contrast agent in human hepatocellular carcinoma.

Dual contrast magnetic resonance imaging (DCMR) with combined use of a negative contrast medium, chondroitin sulfate iron colloid (CSIC), and a positive contrast medium, Gd-DTPA, was attempted in 20 cases of hepatocellular carcinoma. Spin echo T1 weighted and T2 weighted images (T1WI, T2WI), and T1 weighted images 15 min after intravenous injection of Gd-DTPA (0.1 mmol kg-1) were obtained. Within 1 week, these MR studies were repeated within 1 h of intravenous injection of CSIC (23.6 mumol Fe kg-1) under similar conditions. DCMR and the other five imaging techniques were visually evaluated and compared in terms of tumour detectability, tumour spread and qualification of tumours (depiction of inner structure). DCMR was significantly better than Gd-DTPA enhanced T1WI in tumour detectability, and better than Gd-DTPA enhanced T1WI or CSIC enhanced T1WI in depicting tumour spread. In the qualification of tumours, DCMR was significantly better than all the other five imaging techniques. None of the patients in this study showed adverse reactions or significant changes in biochemistry. DCMR is an imaging technique which is able to utilize the characteristics of these contrast agents collectively, and exhibits advantages in grasping the inner structure of tumours, especially in hepatocellular carcinoma.

Long-term prognosis of late spontaneous reperfusion after failed thrombolysis for acute myocardial infarction.

BACKGROUND: Early reperfusion improves left ventricular (LV) function and survival after acute myocardial infarction (MI). Thrombolytic therapy achieves early patency of the infarct artery in about two-thirds of patients. In nearly half of the remaining patients, in whom early reperfusion was not achieved with thrombolytic therapy, the infarct artery might reopen by the time of predischarge angiography. However, the impact of such late spontaneous reperfusion after failed thrombolytic therapy on LV function and long-term survival remained unclear. HYPOTHESIS: This study was undertaken to assess implication of late spontaneous reperfusion after failed thrombolytic therapy on LV function and long-term survival after acute MI. METHODS: The study consisted of 198 patients with anterior acute MI who underwent thrombolytic therapy and predischarge angiography: 160 patients with infarct artery patent early and late after therapy (persistent patency), 17 patients with infarct artery occluded early after therapy but patent at predischarge angiography (late spontaneous reperfusion), and 21 patients with infarct artery occluded early and late after therapy (persistent occlusion). RESULTS: Persistent patency was associated with enhanced improvement in LV ejection fraction (7.7 +/- 11.8%) compared with late spontaneous reperfusion (0.0 +/- 9.6%, p = 0.03) and persistent occlusion (-1.4 +/- 9.7%, p = 0.003). Persistent patency was associated with better long-term survival than with late spontaneous reperfusion (p < 0.001) and persistent occlusion (p < 0.001). Multivariate analysis comparing persistent patency and late spontaneous reperfusion showed that early reperfusion was an independent predictor of long-term survival. CONCLUSION: Late spontaneous reperfusion after failed thrombolytic therapy was associated with poor LV function and long-term survival, emphasizing the importance of early reperfusion.

[A case of leiomyosarcoma of the jejunum with postoperative hepatic encephalopathy].

We report a case of leiomyosarcoma of the jejunum with postoperative hepatic encephalopathy. A 60-year-old man was operated for tumor of the abdomen. He was diagnosed as leiomyosarcoma of the jejunum with disseminated peritoneal metastasis, but no liver metastasis and cirrhosis. A palliative resection of the jejunum was performed. After operation, disturbance of orientation and apraxia with electroencepharographic abnormality and hyperammonemia developed. He was diagnosed as hepatic encephalopathy without lesion of the liver, and died 11 months after surgery. We consider that the portosystemic shunt and bleeding from the digestive tract due to invasion of metastatic lesions caused hepatic encephalopathy.

[Long-term prognosis after reperfusion therapy for acute myocardial infarction in elderly patients].

Although it has been well demonstrated that TIMI grade 3 flow is associated with improved survival after acute myocardial infarction in non-elderly patients, its implication in elderly patients has not been clarified. To assess this issue, 1,115 patients with acute myocardial infarction who underwent coronary angiography within 24 hours after the onset of chest pain were studied: there were 131 elderly patients (age > or = 75 years) and 984 non-elderly patients (age < 75 years). Follow-up was achieved for 1,092 patients (98%). Elderly patients were associated with more female, Killip class > or = 2, 3 vessel disease and non-smokers. Although modality of reperfusion therapy was not different, final TIMI flow grade was less frequently obtained in elderly patients (53% vs 65%, p = 0.005). Elderly patients were associated with higher in-hospital mortality (25% vs 9%, p < 0.001) and lower 10 years cardiac death free rate (p < 0.001). Cox proportional hazards model showed that final TIMI flow grade 3 was an independent predictor of 10 years cardiac death free in elderly patients (odds ratio (OR) = 0.39, 95% confidence interval (CI) = 0.20-0.74, p = 0.004) as well as non-elderly patients (OR = 0.41, 95% CI = 0.29-0.58, p < 0.001). In conclusion, our data suggest that final TIMI grade 3 flow is an important determinant to improve short- and long-term survival after acute myocardial infarction in elderly patients as well as in non-elderly patients.

Single institutional experience of the treatment of angiosarcoma of the face and scalp.

OBJECTIVE: Angiosarcoma is a rare malignant neoplasm with a poor prognosis. A retrospective study was performed to accumulate radiotherapy (RT) data. METHODS: Data from 17 patients with angiosarcoma of the face and scalp (AFS) who were treated with definitive RT between January 1999 and July 2011 were retrospectively analysed. The total radiation dose was 70 Gy, and the fractional doses were 2.0-2.5 Gy. Combined with RT, chemotherapy using docetaxel alone, recombinant interleukin-2 immunotherapy alone and both of these was performed in 10, 4 and 2 patients, respectively. Three patients underwent limited surgery before RT. RESULTS: The response rate was 82%, and the median overall survival (OS) rate was 26 months. Locoregional relapse alone, distant metastasis alone and both of these were confirmed in 4, 5 and 4 patients, respectively. Patients treated with docetaxel showed a better prognosis (p=0.0477), a distant metastasis-free rate (p=0.0063) and a better in-field control rate, although the last was not statistically significant (p=0.1645). CONCLUSION: Definitive RT combined with docetaxel chemotherapy provided an effective approach for treating AFS. ADVANCES IN KNOWLEDGE: Since patients treated with chemoradiotherpy using docetaxel showed better OS and distant metastasis-free rates than those who did not receive docetaxel, it was warranted to continue use of docetaxel. In chemoradiotherapy at a dose of 70 Gy using docetaxel, 2-year in-field control rate was 67%.

Light removes inactivation of the A-type potassium channels in scallop hyperpolarizing photoreceptors.

The properties of light-activated and voltage dependent conductances in the hyperpolarizing photoreceptors of the isolated retina of the giant scallop (Patinopecten yessoensis) have been studied in whole-cell voltage-clamp recordings. Resting membrane potential of the cells was -35 to -60 mV in the dark. Large outward current was maintained during illumination when the cell was voltage clamped at the resting potential. Previous reports have shown that the hyperpolarizing response to light and the light-activated outward current are mediated by an increase of a conductance of K+ channels in the plasma membrane (Gorman and McReynolds, 1974; Gomez and Nasi, 1994a). This report shows that the light-activated K+ channels of this photoreceptor cell generate the voltage-dependent transient outward current in response to depolarizing voltage steps in the dark. The characteristic of this current resembles the typical voltage-dependent transient current (A-current) of molluscan neurons in the kinetics of activation and inactivation, and in the blockage by 4-aminopyridine (4-AP). However, the voltage-dependent transient current during illumination becomes a flat stable form which inactivation process disappeared. We report here that light removes inactivation of the K+ channels which generate the voltage-dependent transient outward currents in the dark.

Attenuation of the no-reflow phenomenon after coronary angioplasty for acute myocardial infarction with intracoronary papaverine.

The no-reflow phenomenon is observed as reduction of coronary blood flow on the angiograms (angiographic no-reflow) after immediate percutaneous transluminal coronary angioplasty (PTCA) in patients with acute myocardial infarction (AMI). To assess whether a potent coronary microvascular dilator--papaverine--could attenuate the no-reflow phenomenon, nine patients with AMI who were found to have angiographic no-reflow after PTCA were studied. Angiographic no-reflow was defined as the Thrombolysis in Myocardial Infarction flow grade 1 or 2 without any mechanical obstructions in the epicardial artery. A bolus dose of 10 mg of intracoronary papaverine was administered, and the flow grade was again evaluated. Intracoronary papaverine caused a significant improvement of the flow grade (p= 0.0152). The number of cineframes that were required for the contrast medium to pass two selected landmarks on the angiograms also significantly decreased (41 +/- 17 frames to 18 +/- 8 frames, p= 0.0039). Thus intracoronary papaverine attenuated angiographic no-reflow that occurred after PTCA for AMI.

Effects of various doses of intracoronary diltiazem on coronary resistance vessels in humans.

We investigated the vasodilative effects of various doses of intracoronary diltiazem on coronary resistance vessels. Nine patients with normal angiograms were studied. A coronary Doppler guide wire was inserted into the left anterior descending coronary artery. Diltiazem, in doses of 0.1 mg, 0.5 mg, 1.0 mg, 2.0 mg and 4.0 mg, was injected into the left coronary artery at 10 min intervals and coronary blood flow velocity was measured. The coronary artery was pretreated with intracoronary nitroglycerin to avoid changes in the cross-sectional area. As a measure of the change in coronary vascular resistance, a coronary vascular resistance index (CVRI) was calculated as mean aortic pressure/coronary blood flow velocity. An injection of diltiazem into the left coronary artery caused a significant dose-dependent decrease in CVRI. A dose of 2.0 mg was the lowest dose on the plateau of the dose-response curve. In conclusion, the injection of diltiazem into the left coronary artery causes a dose-dependent dilatation of coronary resistance vessels, and the maximal effect can be produced with a dose of 2.0 mg.